Screening for FMR-1 premutations in 122 older Flemish males presenting with ataxia

Eur J Hum Genet. 2005 Jan;13(1):121-3. doi: 10.1038/sj.ejhg.5201312.

Abstract

Recently, Hagerman et al described the occurrence of a late-onset neurological disorder in five male carriers of the fragile-X (FMR-1) premutation. The major characteristics of this disorder, designated the Fragile-X Tremor Ataxia Syndrome (FXTAS), are progressive intention tremor, cerebellar ataxia and cognitive decline. Most cases of FXTAS published thus far were ascertained through families with a known fragile-X proband. Since cerebellar ataxia is one of the main cardinal features, we performed FMR-1 premutation screening in 122 male patients, older than 50 years, who were referred to us for testing of the spinocerebellar ataxia (SCA 1, 2, 3, 6, 7) genes and who were found to be negative. In this group of patients, we found five patients with an FMR-1 premutation. In four of them, a definite diagnosis of FXTAS could be made, based on the proposed diagnostic clinical and radiological criteria for FXTAS. In light of these figures, we recommend that FMR-1 analysis should be included in the molecular diagnostic work-up in the group of male ataxia patients older than 50 years.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Ataxia / genetics*
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / genetics*
  • Genetic Testing*
  • Genotype
  • Humans
  • Male
  • Mutation / genetics*
  • Nerve Tissue Proteins / genetics*
  • Neurologic Examination
  • RNA-Binding Proteins / genetics*
  • Tremor / genetics*
  • Trinucleotide Repeat Expansion

Substances

  • FMR1 protein, human
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein